Kinins are potent vasoactive polypeptides which are believed to mediate a variety of acute allergic or inflammatory processes. Kinins are known to have effects on smooth muscle tone and vascular permeability in the lung. A major problem in the understanding of the role of kinins in disease processes existed, however, since we had little or no information about the mechanism by which kinins could be generated by an immune process. Our recently reported studies have shown that kallikrein-like activity can be generated from human basophils as a result of a primary immune reaction, thus providing a potential link between reactions of immediate hypersensitivity and the plasma kinin-generating system. Using the chopped human lung model, we have also observed the immune release of a lung "kallikrein". We propose to study the role of the kallikrein-kinin system in the immediate hypersensitivity reaction. Both the chopped human lung and the leukocyte models have been used in our studies of the relationships between the immediate hypersensitivity and the kallikrein-kinin systems. The studies thus far suggest that the "kallikreins" released by both models are very similar if not identical. These studies will attempt to define the immunochemical, biochemical and pharmacological modulation of the IgE-mediated release of this "kallikrein". Specimens of macroscopically normal human lung recovered from lungs excised for carcinoma will be passively sensitized with homologous antiserum, after which, they will be challenged with ragweed antigen E. Human leukocyte preparations from allergic donors will also be challenged with appropriate antigens. We will investigate the relationship of this newly recognized chemical mediator to other better defined mediators such as histamine. The interaction of this "killikrein" with the better known plasma kallikrein-kinin system will also be examined. BIBLOGRAPHIC REFERENCES: Takahasi, Hidenobu, Webster, Marion E., and Newball, Harold H., Purification of slow reacting substance of anaphylaxis (SRS-A) from human lung. J. Immunology, 117:1039-1044, 1976. Newball, H.H., Allergic reactions. In Yearbook of Science and Technology, D.N. Lapedes, Ed. (McGraw-Hill, N.Y., 1976).